Relationship between apical junction proteins, gene expression and cancer

González‐Mariscal, Lorenza; Miranda, Jael; Gallego-Gutiérrez, Helios; Cano-Cortina, Misael; Amaya, Elida

doi:10.1016/j.bbamem.2020.183278

Cited by 22 publications

(14 citation statements)

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“…The apical junction complex is a cell-cell adhesion system present at the upper portion of the lateral membrane of epithelial cells integrated by the tight junction and the adherens junction. Research is just starting to understand the importance and therapeutic potential of apical junction complex proteins and their role in the early and late stages of cancer ( 125 ). Also in the pathway category is only one gene set associated with OS for CESC patients.…”

Section: Resultsmentioning

confidence: 99%

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

2021

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Although radiotherapy is given to more than 50% of cancer patients, little progress has been made in identifying optimal radiotherapy - drug combinations to improve treatment efficacy. Using molecular data from The Cancer Genome Atlas (TCGA), we extracted a total of 1016 cancer patients that received radiotherapy. The patients were diagnosed with head-and-neck (HNSC - 294 patients), cervical (CESC - 166 patients) and breast (BRCA - 549 patients) cancer. We analyzed mRNA expression patterns of 50 hallmark gene sets of the MSigDB collection, which we divided in eight categories based on a shared biological or functional process. Tumor samples were split into upregulated, neutral or downregulated mRNA expression for all gene sets using a gene set analysis (GSEA) pre-ranked analysis and assessed for their clinical relevance. We found a prognostic association between three of the eight gene set categories (Radiobiological, Metabolism and Proliferation) and overall survival in all three cancer types. Furthermore, multiple single associations were revealed in the other categories considered. To the best of our knowledge, our study is the first report suggesting clinical relevance of molecular characterization based on hallmark gene sets to refine radiation strategies.

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Section: Resultsmentioning

confidence: 99%

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

2021

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“…And in type III epithelial-mesenchymal transition (EMT), the apical junction was disrupted, the apical-basal polarity lost, and the mesenchymal characteristics emerged, finally cells migrated to vessels and traveled to multiply organs and tissues (43). However, some epithelial characteristics were retained, especially the E-cadherin, and the collective migration was observed in metastasis BRCA (44,45). What's more, when in the stage of transplanting to the bone, E-cadherin and Ecadherin adherent junction formed between cancer cells, then the E-cadherin and N-cadherin adherent junction formed between cancer cells and osteoblasts, and cell-cell contact promoted the tumor proliferation via activated mTOR pathway in tumor microenvironment (46).…”

Section: Discussionmentioning

confidence: 99%

Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Breast Invasive Carcinoma

Huang

Zhang

et al. 2021

Front. Oncol.

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BackgroundBone is the most common metastatic site of Breast invasive carcinoma (BRCA). In this study, the bone metastasis-specific regulation network of BRCA was constructed based on prognostic stemness-related signatures (PSRSs), their upstream transcription factors (TFs) and downstream pathways.MethodsClinical information and RNA-seq data of 1,080 primary BRCA samples (1,048 samples without bone metastasis and 32 samples with bone metastasis) were downloaded from The Cancer Genome Atlas (TCGA). The edgeR method was performed to identify differential expressed genes (DEGs). Next, mRNA stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR). To analyze DEGs by classification, similar genes were integrated into the same module by weighted gene co-expression network analysis (WGCNA). Then, univariate and multivariate Cox proportional hazard regression were applied to find the PSRSs. Furthermore, PSRSs, 318 TFs obtained from Cistrome database and 50 hallmark pathways quantified by GSVA were integrated into co-expression analysis. Significant co-expression patterns were used to construct the bone metastasis-specific regulation network. Finally, spatial single-cell RNA-seq and chromatin immunoprecipitation sequence (ChIP-seq) data and multi-omics databases were applied to validate the key scientific hypothesis in the regulation network. Additionally, Connectivity Map (CMap) was utilized to select the potential inhibitors of bone metastasis-specific regulation network in BRCA.ResultsBased on edgeR and WGCNA method, 43 PSRSs were identified. In the bone metastasis-specific regulation network, MAF positively regulated CD248 (R = 0.435, P < 0.001), and hallmark apical junction was the potential pathway of CD248 (R = 0.353, P < 0.001). This regulatory pattern was supported by spatial single-cell RNA sequence, ChIP-seq data and multi-omics online databases. Additionally, alexidine was identified as the possible inhibitor for bone metastasis of BRCA by CMap analysis.ConclusionPSRSs played important roles in bone metastasis of BRCA, and the prognostic model based on PSRSs showed good performance. Especially, we proposed that CD248 was the most significant PSRS, which was positively regulated by MAF, influenced bone metastasis via apical junction pathway. And this axis might be inhibited by alexidine, which providing a potential treatment strategy for bone metastasis of BRCA.

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“…Occludin (OCLN), Plastin-2 (LCP-1) can regulate cytoskeleton transformation [39]. The promotion effect of these two kinds of cells on tumor cell migration and invasion has been con rmed by many studies [40].…”

Section: Proteins Related To Tumor Cell Migration and Invasionmentioning

confidence: 99%

Mechanism of Ferritin Heavy Chain in the Proliferation and Migration of Prostate Cancer Cells

Zhao

Zhang

2021

Preprint

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Ferritin is an important molecule in the regulation of cell proliferation, growth inhibition escape, cell death inhibition and angiogenesis. More and more studies have given evidence of abnormal iron metabolism in tumors. Whether ferritin can be a new type of marker for early diagnosis of tumorous diseases remains to be explored. In this study, we verified the expression level of ferritin heavy chain (FTH) in benign prostatic hyperplasia epithelial cell (BPH-1) and three kinds of PCa cells by Western blotting. Lentivirus was used to construct FTH gene overexpression vector, then construct FTH overexpression PCa cell lines. Meanwhile, LNCaP cells and DU145 cells FTH silent expression prostate cancer cell lines were constructed using Crispr Cas9 technology. Next, clone proliferation experiments, transwell experiments, and scratch experiments were used to verify the cell proliferation, invasion, and migration capabilities of each group of cells with different FTH expression levels. The FTH knockout PC-3 cell (LV-shFTH PC3) has been established in our laboratory. Make full use of the existing results from Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) mass spectrometry technology to analyze differentially expressed protein analysis between LV-shFTH PC3 cells and control cells. Combine GO analysis to select the target protein for subsequent cell protein expression level verification. Our results show that FTH overexpression can promote the proliferation, migration and invasion of prostate cancer cell lines, while FTH knockout causes the opposite result. Combined with mass spectrometry (MS) detection, it is speculated that FTH may trigger changes in cell behavior by regulating the expression of the following proteins: S100A4, CRABP1, S100A2, S100P, GDF15, FAM84B, KRT75, LYRM7, OCLN, LCP1, F2RL1. (The study is not a clinical trial, no registration number and registration date are required)

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Relationship between apical junction proteins, gene expression and cancer

Cited by 22 publications

References 402 publications

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Breast Invasive Carcinoma

Mechanism of Ferritin Heavy Chain in the Proliferation and Migration of Prostate Cancer Cells

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